ABSTRACT/SUMMARY The goal of this proposal is to examine the component and neural processes of cognitive impairment in prostate cancer patients undergoing androgen deprivation therapy (ADT). We will combine neurocognitive testing, clinical assessments, and brain imaging to examine cognitive impairment and its impact on quality of life and identify the structural and functional brain changes that predict the severity of cognitive deficits. Early detection of cognitive side effects of ADT would facilitate clinical decision making in the treatment and care of prostate cancer patients. ADT has proven efficacy in the treatment of many patients with metastatic prostate cancer. However, there is a lack of consensus in the indications for and optimal duration of ADT in prostate cancer patients without metastatic disease. Evidence grows to suggest that ADT may cause cognitive deficits that can have a negative impact on the quality of life in these patients. However, extant studies using traditional neuropsychological testing batteries have not consistently characterized ADT-induced cognitive impairment. It remains unclear whether or when these cognitive deficits will occur in a patient undergoing ADT, whether these deficits pertain broadly or only to specific cognitive domains, and whether the deficits are reversible. Furthermore, there are no established biomarkers that may predict cognitive deficits induced by ADT. Our preliminary findings suggest that cerebral changes may predate clinical manifestations of ADT-induced cognitive impairment. As many prostate cancer patients will receive ADT for many years or for life, according to current treatment protocols, it is of critical importance to identify individuals at risk for cognitive impairment. To this end, we propose to employ longitudinal neurocognitive and clinical assessments, as well as brain imaging, to identify cognitive impairment due to ADT and its impact on quality of life, to examine whether these changes depend on treatment duration and are reversible after a short duration of treatment, and to investigate cerebral markers that may predict cognitive impairment in a large cohort of prostate cancer patients undergoing ADT and control patients not receiving ADT. Our over-arching goal is to thoroughly evaluate the impact of ADT on cognition early during treatment. Studies of cognitive impairment in women receiving chemotherapy have influenced our thoughts about early treatment of breast cancer. Similarly, the findings from this study could enhance our understanding of the risks associated with ADT and inform clinical management of men with prostate cancer.